Schleicher Oliver, Horndasch Annkathrin, Krumbholz Manuela, Sembill Stephanie, Bremensdorfer Claudia, Grabow Desiree, Erdmann Friederike, Karow Axel, Metzler Markus, Suttorp Meinolf
Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
German Childhood Cancer Registry, Division of Childhood Cancer Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Front Oncol. 2022 Sep 29;12:963223. doi: 10.3389/fonc.2022.963223. eCollection 2022.
Pediatric CML is very rare. Before the introduction of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (HSCT) from a donor -if available- was the standard cure attempt. Data on the long-term outcome and health-related quality of life (HRQOL) in former pediatric CML patients undergoing HSCT are lacking.
We investigated long-term survivors' self-reporting to a questionnaire sent out to patients formerly enrolled in pediatric CML-HSCT trials.
Individuals with CML transplanted at age <18 years were identified from the German Childhood Cancer Registry database. Long-term survivors received a questionnaire based on the SF-36 and FACT-BMT asking them to self-report HRQOL issues. (Ethical vote #541_20 B, Medical Faculty, University of Erlangen-Nürnberg).
111/171 (64.9%) individuals survived HSCT long-term and 86/111 (77.5%) fulfilled all inclusion criteria and received the questionnaire. 37/86 (43%) participants (24 female, 13 male, median age at HSCT 12 years [range 2-18], median age at the time of the survey 29 years [range 18-43]) responded after a median follow-up period of 19 years (range 4-27) after HSCT. 10/37 (27%) participants underwent no regular medical follow-up examinations. Self-reported symptoms like chronic graft-versus-host disease (cGvHD)-associated organ impairments and conditioning regimen consequences could causatively not sharply be separated in each case. Complains comprised hypothyroidism (N=11, 30%), infertility (N=9, 24%), lung problems, dry eyes (each N=7, 19%), skin alterations (N=6, 17%), hair problems (N=4, 11%), and sexual dysfunction (N=3, 9%). 10 (27%) participants experienced 13 CML relapses after a median interval from HSCT of 31 months (range 2-93). Only one patient underwent 2nd SCT after failure of relapse treatment with TKIs. Six secondary malignancies (dysplastic melanocytic nevus and ALL, basal cell carcinoma (N=2), rhabdomyosarcoma, and thyroid carcinoma developed in 5 (13%) participants. As assessed by the SF-36 questionnaire, impaired physical health was mainly associated with cGvHD. The mental component summary score showed that also participants without cGvHD scored significantly lower than the general population. When assessed by the FACT-BMT, participants with cGvHD scored significantly lower while participants without cGvHD scored even 5 points higher than the data from controls. 18 (49%) participants considered the sequelae of HSCT an obstacle to education. Out of the total cohort, N=20 (54%), N=7 (19%), N=5 (14%), and N=4 (11%) participants worked full time, part-time, were unemployed, or had not yet finalized their education, respectively. 20 (54%) participants lived as singles, 8 (22%) lived in a partnership, 6 (16%) were married, and 3 (8%) had been divorced. Four (11%) participants reported a total number of 7 children.
This first assessment of HRQOL in former pediatric patients with CML surviving HSCT for more than two decades demonstrates self-reported satisfactory well-being only in the absence of cGvHD. Research-based on self-reported outcomes sheds light on former patients' perspectives and provides an additional layer of valuable knowledge for pediatric and adult hematologists. Regular follow-up examinations are mandatory helping to avoid that late secondary neoplasias, CML-relapse, and disorders forming the broad range of possible long-term consequences of HSCT are not detected too late.
儿童慢性粒细胞白血病（CML）非常罕见。在酪氨酸激酶抑制剂（TKIs）问世之前，若有供体，异基因造血干细胞移植（HSCT）是标准的治愈尝试方法。目前缺乏关于接受HSCT的 former 儿童CML患者的长期结局和健康相关生活质量（HRQOL）的数据。
我们调查了长期存活者对发送给曾参加儿童CML-HSCT试验患者的问卷的自我报告情况。
从德国儿童癌症登记数据库中识别出18岁以下接受CML移植的个体。长期存活者收到一份基于SF-36和FACT-BMT的问卷，要求他们自我报告HRQOL问题。（伦理投票#541_20 B，埃尔朗根-纽伦堡大学医学院）。
111/171（64.9%）个体长期存活HSCT，86/111（77.5%）符合所有纳入标准并收到问卷。37/86（43%）参与者（24名女性，13名男性，HSCT时的中位年龄为12岁[范围2 - 18岁]，调查时的中位年龄为29岁[范围18 - 43岁]）在HSCT后的中位随访期19年（范围4 - 27年）后做出回应。10/37（27%）参与者未进行定期医学随访检查。自我报告的症状，如慢性移植物抗宿主病（cGvHD）相关的器官损伤和预处理方案的后果，在每种情况下都无法明确区分因果关系。抱怨包括甲状腺功能减退（N = 11，30%）、不孕（N = 9，24%）、肺部问题、干眼（各N = 7，19%）、皮肤改变（N = 6，17%）、头发问题（N = 4，11%）和性功能障碍（N = 3，9%）。10名（27%）参与者在HSCT后的中位间隔31个月（范围2 - 93个月）后经历了13次CML复发。只有一名患者在TKI复发治疗失败后接受了第二次SCT。5名（13%）参与者发生了6例继发性恶性肿瘤（发育异常性黑素细胞痣和急性淋巴细胞白血病、基底细胞癌（N = 2）、横纹肌肉瘤和甲状腺癌）。根据SF-36问卷评估，身体健康受损主要与cGvHD相关。心理成分综合评分显示，即使没有cGvHD的参与者得分也显著低于一般人群。当通过FACT-BMT评估时，有cGvHD的参与者得分显著更低，而没有cGvHD 的参与者得分甚至比对照组数据高5分。18名（49%）参与者认为HSCT的后遗症是教育的障碍。在整个队列中，分别有20名（54%）、7名（19%）、5名（14%）和4名（11%）参与者全职工作、兼职工作、失业或尚未完成学业。20名（54%）参与者单身生活，8名（22%）处于伴侣关系，6名（16%）已婚，3名（8%）离婚。4名（11%）参与者报告共有7个孩子。
对存活HSCT超过二十年的 former 儿童CML患者的HRQOL进行的首次评估表明，只有在没有cGvHD的情况下，自我报告的幸福感才令人满意。基于自我报告结果的研究揭示了 former 患者的观点，并为儿科和成人血液学家提供了有价值的额外知识层面。定期随访检查是必不可少的，有助于避免晚期继发性肿瘤、CML复发以及未及时发现构成HSCT广泛可能长期后果的疾病。
